Size Matters in Lymphoma Diagnosis Tissue Biopsy

Pathologists have a perennial reputation for craving more tissue in making any type of diagnosis, and lymphoma is no exception. Speaking as a pathologist, this is completely understandable. Although we are assisted by ancillary studies such as flow cytometry, fluorescence in situ hybridization, and molecular clonality studies,¹  current lymphoma diagnosis and classification continue to rely heavily on morphologic features.^2,3  Tumor cytology can be affected by procedural and tissue processing artifacts such as crush, hemorrhage, and nuclear staining artifacts, and these tend to be more commonly seen in limited biopsies^4,5  (Figure). Moreover, distinguishing malignant lymphomas from reactive conditions depends on analyzing the tissue architecture, which may be difficult to appreciate in a small tissue sample. While a larger excision of lesional tissue can be performed if the initial biopsy is deemed inadequate, the pathologist may perceive pressure to render a definitive diagnosis on the first biopsy in order to spare the patient an additional procedure. Despite these caveats, core needle biopsy (CNB) is becoming an increasingly frequent approach in the initial workup of suspected lymphoma, largely due to lower cost and fewer complications compared to surgical lymph node excision.⁶  A key question remains as to whether these advantages come at the expense of a less accurate diagnosis.

Dr. Charlotte Syrykh and colleagues addressed this question by analyzing the diagnostic performance of lymph node CNB compared to surgical excision in 32,285 patients with clinical suspicion of lymphoma in France. These samples were diagnosed at local institutions (a mix of university, public, and private hospitals and comprehensive cancer centers) and were all reviewed by expert pathologists through the French Lymphopath network.⁷  As expected, the proportion of CNB versus surgical excision increased throughout the study period, from 25 percent of cases in 2010 to 40 percent in 2018. The rate of definitive diagnosis on central expert review was significantly lower with CNB (92.3%) compared to surgical excision (98.1%). A lack of definitive diagnosis was usually due to uncertainty as to the diagnosis of lymphoma (vs. a reactive condition) or the specific lymphoma subtype rather than inadequate material. The concordance rate between local diagnoses and the central expert panel diagnoses was higher on surgical excision (78.8%) compared to CNB (76.9%). When material was referred to pathology experts owing to an initial nondefinitive diagnosis at the local hospital, the rate of the expert review rendering a definitive diagnosis was higher for surgical excisions (93.3%) compared to CNB material (81.4%), mostly due to an increase in the number of cases that could be classified into a specific lymphoma subtype. In particular, peripheral T-cell lymphomas (notably, angioimmunoblastic T-cell lymphoma) and Hodgkin lymphomas presented challenges when encountered on CNB, likely reflecting the importance of tissue architecture in rendering these specific diagnoses. In fact, nodular lymphocyte predominant Hodgkin lymphoma was diagnosed less than half as frequently on CNB compared to surgical excision.